COPD is the fourth leading cause of death in the United States, affecting over 16 million people. This disease is reaching worldwide epidemic proportions and its incidence is rising, particularly in women. More than 85% of COPD in the United States is due to smoking tobacco, and nearly one-quarter of Americans continue to smoke. COPD is a heterogeneous disease defined as airflow obstruction that is not fully reversible and different phenotypes contribute to the severity of the disease. Both genomic and proteomic studies have confirmed that COPD represents a complex and heterogeneous disease that likely involves alterations in the inflammatory cascade, proteolysis apoptotic pathways as well others that have yet to be identified. MicroRNAs (miRNAs) are a family of endogenous, small non-coding RNAs (approximately 21-25 nt long) expressed in many organisms including animals, plants, and viruses. MiRNAs represent a newly discovered layer of gene regulation by targeting mRNA for degradation or inhibition of translation. The primary goals of the proposed study are to identify distinct patterns of microRNA (miRNA) expression in the lung tissue of a well defined cohort of patients with COPD and integrate miRNAs into a systematic approach that defines biological networks across COPD phenotypes. Specific Aim 1: To correlate lung tissue miRNA/mRNA profiling in a cohort of well characterized COPD patients (GOLD 0-4) with disease phenotype. Specific Aim 2: Conduct in vitro analysis of specific miRNAs that correlate with disease phenotype. (End of Abstract) PUBLIC HEALTH RELEVANCE: Project Narrative COPD (Chronic Obstructive Disease) is a lung disease that affects millions of individuals per year and is characterized by progressive, partially irreversible airflow limitation. Tobacco smoke is considered the major risk factor for the development of COPD, however, only a small percentage of smokers (15-20%) ever develop clinically significant COPD. This highlights the importance of genetic susceptibility and other environmental factors as key contributors to disease. We propose to take a multiplatform approach that integrates both microRNA and mRNA expression patterns to study well defined clinical phenotypes of disease in COPD.